13-101786928-C-G

Variant names:

• chr13-101786928-C-G
• rs9300694
• NM_004115.4:c.409-60118G>C

Variant summary

Our verdict is Benign. The variant received -12 ACMG points: 0P and 12B. BP4_Strong BA1

The NM_004115.4(FGF14):​c.409-60118G>C variant causes a intron change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.906 in 152,122 control chromosomes in the GnomAD database, including 63,920 homozygotes. In-silico tool predicts a benign outcome for this variant. No clinical diagnostic laboratories have submitted clinical-significance assessments for this variant to ClinVar.

• Frequency: Genomes: 𝑓 0.91 (63920 hom., cov: 31)
• Consequence: FGF14 NM_004115.4 intron
• Clinical Significance: Not reported in ClinVar
• Conservation: PhyloP100: 0.0950
• Publications: 1 publications found

Genes affected

FGF14 (HGNC:3671): (fibroblast growth factor 14) The protein encoded by this gene is a member of the fibroblast growth factor (FGF) family. FGF family members possess broad mitogenic and cell survival activities, and are involved in a variety of biological processes, including embryonic development, cell growth, morphogenesis, tissue repair, tumor growth and invasion. A mutation in this gene is associated with autosomal dominant cerebral ataxia. Alternatively spliced transcript variants have been found for this gene. [provided by RefSeq, Jul 2008]

FGF14 Gene-Disease associations (from GenCC):

• spinocerebellar ataxia 27A

  Inheritance: AD Classification: STRONG Submitted by: Labcorp Genetics (formerly Invitae)
• spinocerebellar ataxia type 27

  Inheritance: AD Classification: MODERATE, SUPPORTIVE Submitted by: Ambry Genetics, Orphanet
• autosomal recessive cerebellar ataxia

  Inheritance: AR Classification: LIMITED Submitted by: Ambry Genetics

ACMG classification

Our verdict: Benign. The variant received -12 ACMG points.

• BP4: Computational evidence support a benign effect (BayesDel_noAF=-0.96).
• BA1: GnomAd4 highest subpopulation (EAS) allele frequency at 95% confidence interval = 0.988 is higher than 0.05.

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	MANE	Protein	UniProt
FGF14	NM_004115.4	c.409-60118G>C		intron_variant	Intron 3 of 4	ENST00000376143.5	NP_004106.1

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	TSL	MANE	Protein	Appris	UniProt
FGF14	ENST00000376143.5	c.409-60118G>C		intron_variant	Intron 3 of 4	1	NM_004115.4	ENSP00000365313.4

Frequencies

GnomAD3 genomes AF: 0.906 AC: 137736 AN: 152006 Hom.: 63903 Cov.: 31

Gnomad AFR AF: 0.685

Gnomad AMI AF: 0.992

Gnomad AMR AF: 0.964

Gnomad ASJ AF: 0.995

Gnomad EAS AF: 1.00

Gnomad SAS AF: 0.975

Gnomad FIN AF: 0.999

Gnomad MID AF: 0.959

Gnomad NFE AF: 0.994

Gnomad OTH AF: 0.932

We have no GnomAD4 exomes data on this position. Probably position not covered by the project.

GnomAD4 genome AF: 0.906 AC: 137800 AN: 152122 Hom.: 63920 Cov.: 31 AF XY: 0.909 AC XY: 67582 AN XY: 74372

African (AFR) AF: 0.685 AC: 28381 AN: 41442

American (AMR) AF: 0.964 AC: 14730 AN: 15276

Ashkenazi Jewish (ASJ) AF: 0.995 AC: 3454 AN: 3470

East Asian (EAS) AF: 1.00 AC: 5162 AN: 5162

South Asian (SAS) AF: 0.975 AC: 4692 AN: 4814

European-Finnish (FIN) AF: 0.999 AC: 10602 AN: 10608

Middle Eastern (MID) AF: 0.959 AC: 282 AN: 294

European-Non Finnish (NFE) AF: 0.994 AC: 67619 AN: 68028

Other (OTH) AF: 0.932 AC: 1973 AN: 2116

Alfa AF: 0.948 Hom.: 8100

Bravo AF: 0.896

Asia WGS AF: 0.970 AC: 3371 AN: 3476

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.3

Name	Calibrated prediction	Score	Prediction
BayesDel_noAF	Benign	-0.96
CADD	Benign	5.0
DANN	Benign	0.71
PhyloP100		0.095
Mutation Taster		=100/0	polymorphism (auto)

Splicing

Name	Calibrated prediction	Score	Prediction
SpliceAI score (max)		0.0		Details are displayed if max score is > 0.2

Find out detailed SpliceAI scores and Pangolin per-transcript scores at spliceailookup.broadinstitute.org

Other links and lift over

dbSNP: rs9300694; hg19: chr13-102439278;